This is a proposal for continuation of the Midcareer Investigator Award in Patient-Oriented Research (K24) for Lee H. Harrison, MD, at the University of Pittsburgh. The principal aims are to 1) provide mentorship in patient-oriented research, 2) provide leadership and direction to the Infectious Diseases Epidemiology Research Unit (IDERU) and Public Health Infectious Diseases Laboratory (PHIDL) at the University of Pittsburgh, and 3) support Dr. Harrison's clinical and epidemiologic research on serious bacterial pathogens. As with the first five years of the award, a major focus of the next five years will be to provide mentorship to infectious diseases fellows, clinicians obtaining degrees at the Pitt Graduate School of Public Health, and junior faculty members in the Department of Medicine. This will be accomplished by having dedicated time for mentorship and by making available substantial resources to trainees, including: the resources of the IDERU, which has a broad research portfolio of clinical, epidemiologic and molecular epidemiologic studies of bacterial diseases, and PHIDL, a cutting-edge molecular epidemiology laboratory, at the University of Pittsburgh;two NIH Fogarty International Center research training grants, one on the epidemiology and molecular epidemiology of serious bacterial diseases and another on HIV/AIDS;and the resources of the CDC-funded Maryland Active Bacterial Core Surveillance (ABCs) project, which is based at Johns Hopkins University and led by Dr. Harrison. One of the many patient-oriented studies that will be conducted during the award period is a project entitled, "Real-Time PCR for Diagnosis of Culture Negative Bacterial Meningitis in Brazil". This will be a prospective study of culture-negative meningitis patients seeking care at 13 hospitals in Sao Paulo and Campinas, Brazil, were over half of pyogenic meningitis patients are culture negative. The specific aims are to 1) characterize the proportion of Brazilian patients with culture-negative bacterial meningitis using RT-PCR for H. influenzae, S. pneumoniae, and N. meningitidis, 2) identify risk factors for being culture negative/RT-PCR positive, and 3) determine the performance characteristics of RT-PCR when incorporated into routine public health surveillance. This study has the potential to improve clinical care of bacterial meningitis patients in Brazil and provide policy makers with information for informed decisions about incorporation of new conjugate vaccines into the Brazilian immunization schedule.